The knowledge of the complexity of the machinery that participates in gene expression has significantly changed with the finding that a tight coupling exists between transcriptional and post-transcriptional processes. The carboxy-terminal domain of the polII large subunit drives on the nascent transcripts several factors required for post-transcriptional events: capping, splicing, polyadenylation. We are interested in studying the RNA-protein interactions that occur during the early phases of transcription and commit the primary transcript to its specific maturation fate. In particular, we are studying the biosynthesis of the complex class of small non coding RNAs including miRNAs, snoRNAs and snRNAs

Biosynthesis and function of miRNAs

In the last years a new network of regulatory circuits operating at the post-transcriptional level has been disclosed with the discovery of a complex class of non-coding RNAs of microscopic size (miRNAs). These molecules control gene reprogramming occurring during development and cell differentiation by regulating translation and stability of specific target mRNAs. We are interested in the following aspects of miRNA research: i) identify the regulatory regions required for their transcription and 3 end formation; ii) understand the mechanisms of translational and stability control; iii) study their role in the control of cell differentiation with specific interest in hematopoietic and neuronal differentiation.

Therapeutic RNAs

Antisense, ribozymes, aptamers and, more recently, siRNAs are modified activities of natural RNAs that can be utilized to control gene expression in a sequence-specific way. In the last years we have exploited some of these RNA activities for the gene therapy of different genetic diseases. One succeful application has been the use of antisense molecules for the gene therapy of the Duchenne Muscular Dystrophy. Recent work in the mdx dystrophic mouse has shown that AAV recombinant viruses carrying antisense-expression cassettes are very effective in systemic in vivo delivery of therapeutic sequences to affected muscles and in restoring both dystrophin synthesis and muscular functionality. In the future we intend to extend the use of other small non coding RNAs (siRNAs and miRNAs) to the therapy of different gene disorders.